The acute and chronic myocardial effects of chemotherapeutic drugs will be evaluated in conscious, chronically instrumented dogs. The reversibility of these toxic effects, additive effects of various drugs, factors intensifying the toxic effects, and methods for protection of the myocardium against these toxic effects will be investigated. In preliminary operations the left ventricle of mongrel dogs will be instrumented with pressure and dimension transducers. Left ventricular pressures, dimensions, and parameters of LV contractile state will be monitored during and after the administration of clinically equivalent doses of adriamycin and its cogeners cyclophosphamide, 5 aza-cytidine, and experimental agents. After the induction of chronic myocardial depression or after the administration of a cumulative dose equivalent to that employed clinically, LV dynamics will be monitored on a regular schedule for 3 to 6 months. During the "recovery phase" various therapeutic modalities will be evaluated for their effectiveness in alleviating the myocardial dysfunction induced by the drugs. The myocardial toxicity of chemotherapeutic drugs will be evaluated in some dogs with prior myocardial dysfunction induced by chronic administration of adriamycin. Methods for mycardial protection during the administration of adriamycin will consist of: reduction of coronary blood flow and thus the dose to the myocardium by decreasing myocardial oxygen requirements; reduction in any inflammatory or autolytic processes induced by initial drug action on the myocardium; methods to diminish myocardial intracellular calcium overload. It is anticipated that the knowledge gained from these protocols will be immediately applicable in the treatment of patients with cancer and that the proposed experimental model will be available to evaluate newly developed chemotherapeutic drugs.